The investigations in this plan are designed to reveal whether three small hypothalamic peptides with known endocrine roles may also function as central neurotransmitters. Thyrotropin releasing hormone, luteinizing hormone releasing hormone, and somatotropin release inhibiting factor (or somatostatin) have been shown to have behavioral effects, to be widely distributed in brain, and to be active iontophoretically on central neurons. A primary aim of the proposed research is to see if in addition these peptides bind to specific receptor sites in brain. Binding studies with radioactive peptides will be performed to detect such sites and to characterize them pharmacologically for comparison with pituitary receptors and with behavioral and iontophoretic data. Further studies will focus on peptide uptake, biosynthesis, breakdown, storage and release in extrahypothalamic brain regions. These studies will be looking for characteristics suggestive of a peptide neurotransmitter role as distinct from a possible neuromodulator role and from the peptides' specialized neuroendocrine role in the hypothalamus. In Addition to binding, techniques will include subcellular fractionation, incubation of synaptosomes and tissue fragments with radioactive peptides and amino acids, column and thin layer chromatography and electrophoresis, and radioimmunoassay.